Zinc for the prevention or treatment of acute viral respiratory tract infections in adults: a rapid systematic review and meta-analysis of randomised controlled trials

Abstract

ObjectiveTo evaluate the benefits and risks of zinc formulations compared with controls for prevention or treatment of acute viral respiratory tract infections (RTIs) in adults.MethodSeventeen English and Chinese databases were searched in April/May 2020 for randomised controlled trials (RCTs), and from April/May 2020 to August 2020 for SARS-CoV-2 RCTs. Cochrane rapid review methods were applied. Quality appraisals used the Risk of Bias 2.0 and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach.ResultsTwenty-eight RCTs with 5446 participants were identified. None were specific to SARS-CoV-2. Compared with placebo, oral or intranasal zinc prevented 5 RTIs per 100 person-months (95% CI 1 to 8, numbers needed to treat (NNT)=20, moderate-certainty/quality). Sublingual zinc did not prevent clinical colds following human rhinovirus inoculations (relative risk, RR 0.96, 95% CI 0.77 to 1.21, moderate-certainty/quality). On average, symptoms resolved 2 days earlier with sublingual or intranasal zinc compared with placebo (95% CI 0.61 to 3.50, very low-certainty/quality) and 19 more adults per 100 were likely to remain symptomatic on day 7 without zinc (95% CI 2 to 38, NNT=5, low-certainty/quality). There were clinically significant reductions in day 3 symptom severity scores (mean difference, MD −1.20 points, 95% CI −0.66 to −1.74, low-certainty/quality), but not average daily symptom severity scores (standardised MD −0.15, 95% CI −0.43 to 0.13, low-certainty/quality). Non-serious adverse events (AEs) (eg, nausea, mouth/nasal irritation) were higher (RR 1.41, 95% CI 1.17 to 1.69, NNHarm=7, moderate-certainty/quality). Compared with active controls, there were no differences in illness duration or AEs (low-certainty/quality). No serious AEs were reported in the 25 RCTs that monitored them (low-certainty/quality).ConclusionsIn adult populations unlikely to be zinc deficient, there was some evidence suggesting zinc might prevent RTIs symptoms and shorten duration. Non-serious AEs may limit tolerability for some. The comparative efficacy/effectiveness of different zinc formulations and doses were unclear. The GRADE-certainty/quality of the evidence was limited by a high risk of bias, small sample sizes and/or heterogeneity. Further research, including SARS-CoV-2 clinical trials is warranted.PROSPERO registration numberCRD42020182044.

Zinc Intakes and Health Outcomes: An Umbrella Review

“…After receiving supplementary zinc over 20 mg each day, adults with acute viral respiratory tract infections (including COVID-19) would be 1.83 times more likely to recover before the placebo (HR: 1.83, 95% CI: 1.07, 3.13) as well as have a clinically significant reduction in mean duration (MD: −2.05, 95% CI: −3.50, −0.59) and day 3 symptom scores (MD: −1.20, 95% CI: −1.74, −0.66) ( 10 ). Yet average daily acute viral respiratory tract infection symptom scores in adults (MD: −0.15, 95% CI: −0.43, 0.13) ( 10 ) and symptoms of the common cold in the first week in the general population (OR: 0.52, 95% CI: 0.25, 1.20) ( 53 ) might not get improvement when they were supplemented with zinc.…”

“…To be more specific, the incidence and prevalence of pneumonia were 13% (RR: 0.87, 95% CI: 0.81, 0.94) and 41% (RR: 0.59, 95% CI: 0.35, 0.99) lower in the zinc supplemented children, respectively (52). However, low dosages of zinc failed to neither significantly attenuate the risk of lower respiratory tract infections (RR: 0.78, 95% CI: 0.49, (10). Yet average daily acute viral respiratory tract infection symptom scores in adults (MD: −0.15, 95% CI: −0.43, 0.13) (10) and symptoms of the common cold in the first week in the general population (OR: 0.52, 95% CI: 0.25, 1.20) (53) might not get improvement when they were supplemented with zinc.…”

“…Two authors (JL and DHC) independently extracted the following data from eligible studies: (1) first author and publication year, (2) population, (3) the number of cases and participants in each study, (4) category of exposure (dietary and supplementary zinc), (5) outcome, (6) the estimated summary effect (ES, MD, OR, RR, SMD, and WMD), (7) corresponding 95% confidence intervals (CIs), (8) the number of included studies, (9) study design (cohort, case-control, cross-sectional and RCT), (10) type of comparisons (<20 mg/day Vs. never, >20 mg/day vs. never, highest vs. lowest and increment of 5 mg or 100 mg of dietary or supplementary zinc), (11) effect model (fixed or random), (12) I 2 statistic value, (13) Cochran's Q test P-value, (14) Egger's test P value. If more than one outcome was reported in one article, we extracted each outcome respectively.…”

“…From another aspect, zinc deficiency was gradually thought to be the risk factor of anemia (8), cognitive disorders (8), gastrointestinal dysfunction (1), hepatosplenomegaly (1), hypogonadism (8,9), and so on. Furthermore, zinc therapy is to some certain extent applied in clinical treatment and prevention of COVID-19 (10), which further proved the importance of zinc. Zinc is distributed in a wide range of food, including meat (fish, red meat, and meat products), grains, cereals, dairy products, and dietary supplements (11).…”

“…Until now, the associations between human zinc intakes and a wide range of health outcomes have been explored extensively. Nevertheless, there have been inconsistent conclusions about some specific outcomes, for instance, acute respiratory tract infection (including COVID-19) (10,(15)(16)(17)(18)(19)(20). Besides, the effect of zinc can be dangerous sometimes.…”